Big deal. The stated risk is 1 in a 1000. The reality is more like 1 in 10,000. The sensationalism has got to stop.

11:15 am October 30, 2008

Steve Walker wrote :

Actually, the risk is at about 1 in 4,000 right now and going down from the 1 in a 1,000 the FDA thought was acceptable a couple of years ago, with only one of the 6 patients reported to have developed PML, dying.

Experts don't even know if PML is caused by Tysabri. MS is an autoimmune disease in which the immune system attacks a substance called myelin that coats nerve cells. The drugs that most effectively treat MS (and Tysabri is a very, very effective drug that stops and even reverses the debilitating effects of MS in many patients) modulates the immune system to control the attacks. The truth is, Tysabri is an exceedingly safe drug when compared to the risks of the disease, and to many other drugs approved to treat serious and life-threatening disease that are not restricted by FDA regarding prescribing at all.

To prove a real risk using FDA's hopelessly obsolete statistical testing methods that PML is caused by Tysabri would require running a trial with at least 100,000 MS patients (a very tall order to find 100,000 patients who would qualify and choose to enroll - it would take many years and likely ultimately prove impossible), half getting placebo (which would allow their disease to progress and cripple them), under blinded randomized conditions with no cross over to the active drug upon progression, for at least five years of patient experience for most of the enrolled patients. A trial this size would take years to enroll, which means waiting even longer for 5 years of patient experience that would stretch the trial results out to maybe ten or more years before a statistically significant data set would emerge in the form of about 10 to 20 PML cases occurring in the study (including both arms). Note that even then it would only be statistically significant if there was a substantial imbalance in the number of cases in the two arms.

Also take into account that many patients would drop out of the trial due to death, disease progression, better treatment options, or simply getting tired of watching their disease progress while being deceived about whether they are getting the drug or a placebo.

I suspect I have underestimated both the size and duration of the trial that would be needed.

What would we learn? Statisticians would then tell us that PML is extremely rare in MS patients receiving either Tysabri or placebo (something we already know), and they might (and I stress might) be able to tell us whether it is slightly more common in patients receiving Tysabri compared to the patients not getting it (or vice versa).

In the meantime, most of the patients in the placebo arm (those who decided to stay in the trial - which would probably be close to none of them) would have seen their disease progress, and some would have been crippled by their disease, while those getting the drug would have seen the progression of their disease controlled and even reversed. Finally, the results would be hopelessly obsolete, because there would be newer drugs for MS on the market, understanding of the disease and how to treat it would have progressed, and the use of Tysabri would have certainly changed.

Obviously this trial is unnecessary and would be grossly unethical.

It is important to put the reporting of a single case (or even 6 out of 35,500) of PML into perspective, and unfortunately today, the WSJ didn't do a very good job of that.

This is a big deal only if one is the patient, or a family member or close friend of one of the patients, who had the misfortune of being the one who contracted PML. Of the 6 people taking Tysabri who have also contracted PML, only one has died, and some have recovered.

Oh, one more thing. People who don't have MS, and who don't take Tysabri, also very rarely develop PML. we don't know why that happenms either. No one knows what the background incidence is in the general population, or in patients with MS, and FDA's obsolete trial methods cannot tell us.

Take a deep breath, and consider the following: perspective, perspective, perspective!. It's important, especially if one has MS.

Steve Walker
Abigail Alliance

11:23 am October 30, 2008

william t beyha wrote :

yawn. plenty of people being born and becoming dead. supply and demand= money.
for those of you interested in the how and why of autoimmune diseases please do a pubmedsearch for faustman dl and read at faustmanlab.org.
the mechanisms and safety and adequacy of current drugs for autoimmune diseases is more than seriously called into question with her work.
after reading her work decide for yourself on the risks and benefits. lawyers should read carefully also. if you have a friend that has an autoimmune disease and you would like to see them have more than one, read faustman's papers and push for current drugs.
you can make good money betting on the occurrence of more autoimmune diseases after taking current drugs.
life death money all one in the same. get your bets down and enjoy while you can before you ...

3:16 pm October 30, 2008

FitzPatrick wrote :

One needs to keep in mind that there is alot that is not known about PML, especially in a non-HIV population. More specifically, we do not know what the prevalence of PML in people with autoimmune diseases. The reason for this is that PML was not associated with autoimmune disease, like MS and the signs & symptoms can be non-descript which can lead to the diagnosis of another neuroinfectious dx. Basically, you need be looking for it and associated with diseases where there was immunosuppression. To conduct a PML registry in Tysabri or other immunomodulatory drugs would not be feasible, because it is a rare disease and the number of patients required to be statistically significant would take too long and would not be practical. This is the biggest challenge in understanding PML in autoimmune diseases:
1. Is it an emergent neuroinfection dx in certain susceptible patients with certain intrinsic risk factors or immune system polymorphisms.
2. Is it a disease-drug association? If we could better understand the potential mechanisms that could cause this rare disease.
3. Is it a disease-disease-drug association? Could an underlying disease be associated with predisposing patients.
4. SInce all TYSABRI patients have had prior exposure of at least INFB, Copaxone, etc, could these drugs cause a sequential/contributing stress in certain patients
There is no easy answer. The question is can more discrete risk factors for PML be identified that are specific for autoimmune disease (e.g., MS). This would not only be important for Tysabri but for other immunomodulatory drugs that have reported PML cases. If so, this may allow for physicians and other stakeholders to screen patients and determine more definitively which patients should or should not receive the drug. Thus, the drugs benefit-risks can be better evaluate for each patient.
While PML is a very rare disease, it has a high mortality with no known cure. One should not dismiss this lightly. As more MS drugs come on the market that have similar efficacy to Tysabri (e.g., Campath) one will need to evaluate which one would be better for the patient by evaluating the B/R profile.

11:59 pm November 2, 2008

got MS? read the work of Denise L Faustman wrote :

autoimmune diseases are neither being correctly treated nor explicated. faustman's work calls into great question the safety, efficacy, adequacy of warnings, and scientific rational for many drugs being used to treat autoimmune diseases.
read the results of pubmed.org
search for faustman dl and look at faustmanlab.org.

william t beyha

11:10 pm November 11, 2008

tootsie wrote :

from italy:I have multiple sclerosis
and, if it were your mother, sister, wife, brother, father, a nephew TYSABRI take?
talking so?
I do not think ... ciao-ciao ;-)

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